The proposed work is designed to determine the role of hyperthermia-induced damage to replicating chromatin in heat-induced cell inactivation and radiosensitization of cultured mammalian cells. With regard to heat-induced cell death, the extent to which hyperthermia causes alterations in the structure of replicating chromatin or alterations in the rate, or extent, of initiation and /or elongation of DNA during synthesis will be determined. With regard to radiosensitization, the degree to which ionizing radiation increases heat-induced alterations in the structure of the replication apparatus or in the rate at which it functions will be determined. All biochemical findings will be correlated with cell inactivaion under similar treatment protocols.